Pathophysiology Mechanisms: Lipids Flashcards
Focus on the mechanisms behind each condition — how they affect lipid metabolism, and why they lead to the symptoms and test results. (13 cards)
Secondary Hyperlipidaemia (due to Hypothyroidism)
Reduced thyroid hormone levels increase lipoprotein production in the liver, leading to elevated cholesterol and triglycerides. The lack of thyroid hormones alters lipid metabolism, exacerbating dyslipidaemia.
Memory Hook: “Liver on overtime, pushing out lipids.”
Primary Hypothyroidism
Mechanism:
In hypothyroidism, decreased thyroid hormone levels lead to reduced LDL receptor activity in the liver. This results in poor clearance of LDL from the bloodstream, causing LDL to accumulate, thus raising total cholesterol levels.
Additionally, hypothyroidism causes a slower metabolism, leading to elevated cholesterol levels overall.
Memory Hook: “A closed toll booth traps the LDL traffic.”
Remnant Hyperlipoproteinaemia (Familial Dysbetalipoproteinaemia)
Mechanism:
A mutation in the ApoE gene (often the ApoE2 variant) impairs the liver’s ability to clear remnant lipoproteins (such as IDL and chylomicron remnants). These lipoproteins build up in the blood, raising cholesterol and triglyceride levels.
Memory Hook: “A recycling center that can’t clear the waste.”
Secondary Hypertriglyceridaemia (due to Chronic Alcohol Consumption and Metabolic Syndrome)
Mechanism:
Chronic alcohol intake and metabolic syndrome increase the liver’s production of VLDL (very-low-density lipoproteins), which leads to elevated triglyceride levels. Alcohol also inhibits lipoprotein lipase (LPL), reducing triglyceride clearance from the bloodstream.
Memory Hook: “The liver’s a brewery churning out triglycerides.”
- Heterozygous Familial Hypercholesterolaemia (HeFH) due to ApoB-100 Mutation
In HeFH, the mutation in the ApoB-100 protein impairs LDL receptor recognition, preventing LDL particles from being cleared from the bloodstream. This results in high LDL cholesterol levels.
Memory Hook: “The LDL delivery truck can’t find its address.”
Type 2 Diabetes Mellitus with Secondary Hypertriglyceridaemia
Mechanism:
Insulin resistance in type 2 diabetes leads to increased hepatic VLDL production and impaired clearance of triglycerides, causing elevated triglyceride levels in the blood. Insulin resistance also exacerbates hyperlipidaemia by increasing the production of fatty acids.
Memory Hook: “The highway’s congested with triglycerides.”
Familial Combined Hyperlipidaemia (FCHL)
FCHL involves an overproduction of ApoB-containing lipoproteins by the liver, including VLDL and LDL. This leads to elevated levels of both triglycerides and LDL cholesterol in the blood.
Memory Hook: “The liver is a factory producing too many lipoproteins.”
Familial Hypertriglyceridaemia
Mechanism:
In familial hypertriglyceridaemia, mutations in the lipoprotein lipase (LPL) enzyme reduce its activity, impairing the clearance of triglycerides from the bloodstream. This results in elevated triglyceride levels.
Memory Hook: “The delivery service (lipoprotein lipase) is understaffed.”
Lipoprotein(a) Excess
Mechanism:
Elevated levels of lipoprotein(a), a modified form of LDL, are genetically determined and can increase the risk of cardiovascular diseases. Lp(a) impairs fibrinolysis (the breakdown of blood clots), promoting clot formation in arteries.
Memory Hook: “An extra load of cargo makes LDL harder to transport.”
Nephrotic Syndrome
Mechanism:
Nephrotic syndrome leads to the loss of proteins in the urine, which results in the liver producing more lipoproteins to compensate. This overproduction leads to elevated levels of cholesterol and triglycerides.
Memory Hook: “The liver is running overtime, cranking out lipoproteins.”
Cushing’s Syndrome
Mechanism:
Elevated cortisol in Cushing’s syndrome promotes gluconeogenesis (production of glucose from non-carbohydrate sources), which leads to hyperglycaemia and insulin resistance. Cortisol also increases the production of lipids and reduces the clearance of triglycerides, causing elevated cholesterol and triglycerides.
Memory Hook: “Stress factory overproduces lipids.”
Cholestatic Liver Disease
Mechanism:
Impaired bile flow in cholestatic liver disease leads to the accumulation of lipoprotein-X, which increases cholesterol levels. Additionally, the liver produces more cholesterol in response to bile acid dysfunction, leading to hypercholesterolaemia.
Memory Hook: “A blocked drain backs up cholesterol.”
Obstructive Liver Disease
Mechanism:
Similar to cholestatic liver disease, obstructive liver disease leads to a reduction in bile flow, causing cholesterol to accumulate in the bloodstream. This results in elevated cholesterol levels.
Memory Hook: “A clogged pipe causes cholesterol to pile up.”
